Dimethylformamide → (2R)-3-(7-methyl-1H-indazol-5-yl)-1-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)-1-oxopropan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

HRID 501961

반응식

HRID 501961 반응식
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:11][C@@H:12]([O:16][C:17]([N:19]2[CH2:24][CH2:23][CH:22](C3C(=O)NC4C(C=3)=CC=CC=4)[CH2:21][CH2:20]2)=[O:18])[C:13]([OH:15])=O)[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.[CH:36](N(C(C)C)CC)([CH3:38])[CH3:37].Cl.Cl.[CH3:47][N:48]1[CH2:53][CH2:52][C:51]2([CH2:58][CH2:57][NH:56][CH2:55][CH2:54]2)[CH2:50][CH2:49]1.C1CN([P+](ON2N=[N:83][C:78]3[CH:79]=[CH:80][CH:81]=[CH:82][C:77]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CN(C)C=[O:95]>ClCCl>[O:95]=[C:38]1[C:36]([CH:22]2[CH2:21][CH2:20][N:19]([C:17]([O:16][C@H:12]([CH2:11][C:4]3[CH:5]=[C:6]4[C:10](=[C:2]([CH3:1])[CH:3]=3)[NH:9][N:8]=[CH:7]4)[C:13](=[O:15])[N:56]3[CH2:57][CH2:58][C:51]4([CH2:52][CH2:53][N:48]([CH3:47])[CH2:49][CH2:50]4)[CH2:54][CH2:55]3)=[O:18])[CH2:24][CH2:23]2)=[CH:37][C:77]2[C:78](=[CH:79][CH:80]=[CH:81][CH:82]=2)[NH:83]1

참가 물질

7

반응물 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 59424312(R)-3-(7-Methyl-1H-indazol-5-yl)-2-(4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carbonyloxy)propanoic acidHCID 675237033-Methyl-3,9-diazaspiro[5.5]undecane dihydrochloride

생성물 1

HCID 11657395(2R)-3-(7-methyl-1H-indazol-5-yl)-1-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)-1-oxopropan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

To a solution of (R)-3-(7-methyl-1H-indazol-5-yl)-2-(4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carbonyloxy)propanoic acid (50 mg, 0.11 mmol), diisopropylethylamine (37 UL, 0.21 mmol), and 3-methyl-3,9-diaza-spiro[5.5]undecane dihydrochloride (65.2 mg, 2.0 equiv) in dimethylformamide (0.50 mL) and dichloromethane (0.50 mL) at 0° C. was added PyBOP® (57.6 mg, 0.11 mmol). The reaction was stirred at 0° C. for 4 h. The reaction was concentrated and purified by column chromatography (95:5:1 to 90:10:1 dichloromethane/methanol/triethylamine). The resulting residue was dissolved in 5% methanol/dichloromethane and passed through a basic alumina column to give 52 mg (77%) as a white powder. 1H-NMR (CD3OD, 500 MHz) δ 0.12-0.55 (m, 1H), 0.85-1.70 (m, 1H), 1.85 (m, 2H), 2.05-2.42 (m, 8H), 2.50 (s, 3H), 2.73-3.30 (m, 8H), 3.65 (bs, 1H), 4.00-4.43 (m, 2H), 5.46 (dd, J=7.6, 7.6, 1H), 7.07 (s, 1H), 7.17 (m, 1H), 7.27 (m, 1H), 7.38-7.46 (m, 2H), 7.50 (bs, 0.5H), 7.58 (m, 1H), 7.65 (bs, 0.5H), 7.96 (s, 1H). Mass spec.: 625.33 (MH)+.

후처리

  1. concentrationThe reaction was concentrated
  2. custompurified by column chromatography (95:5:1 to 90:10:1 dichloromethane/methanol/triethylamine)
  3. dissolutionThe resulting residue was dissolved in 5% methanol/dichloromethane
  4. customto give 52 mg (77%) as a white powder

출처 및 근거

ORD 기록
ord-07d9d5043afc48598d8d6d676a5b0271
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07772244B2

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